Ethylenediamine → HCID 53379340, compound

HRID 1617421Notes

Reaction equation

HRID 1617421 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:10][C:9]([CH2:33][C:34]#[N:35])([N:11]3[CH:15]=[C:14]([C:16]4[C:17]5[CH:24]=[CH:23][N:22](COCC[Si](C)(C)C)[C:18]=5[N:19]=[CH:20][N:21]=4)[CH:13]=[N:12]3)[CH2:8]2)[CH2:3][CH2:2]1.Cl[C:37]([O:39][CH2:40][CH2:41][CH3:42])=[O:38].C(Cl)Cl.C(O)(C(F)(F)F)=O.C(N)CN>CO>[C:34]([CH2:33][C:9]1([N:11]2[CH:15]=[C:14]([C:16]3[C:17]4[CH:24]=[CH:23][NH:22][C:18]=4[N:19]=[CH:20][N:21]=3)[CH:13]=[N:12]2)[CH2:8][N:7]([CH:4]2[CH2:3][CH2:2][N:1]([C:37]([O:39][CH2:40][CH2:41][CH3:42])=[O:38])[CH2:6][CH2:5]2)[CH2:10]1)#[N:35]

Participants

7

Reactant 5

HCID 3301EthylenediamineHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 7998Propyl chloroformateHCID 67391103{1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

Product 1

HCID 53379340HCID 53379340, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of {1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (0.010 g, 0.020 mmol) and propyl chloroformate (3.0 μL, 0.026 mmol) in methylene chloride (1 mL, 20 mmol) was stirred for 1.5 h. TFA, 1 mL, was added. After 1 hour, the solvent was removed by rotary evaporation to give an oil. The oil was dissolved in 1 mL MeOH and 50 microL ethylenediamine was added. After 1 hour, the reaction was purified by prep-HPLC (pH10) using a Waters XBridge C18, 5 μm particle size, 19×100 mm; mobile phase system: aqueous (0.1% NH4OH)/acetonitrile; flow rate: 30 mL/min; separation gradient: 40-60% B in 5 min to give 5.3 mg white solid (58%). 1H NMR (400 MHz, DMSO): δ 12.13 (1H, br); 8.83 (1H, s); 8.7 (1H, s); 8.42 (1H, s); 7.61 (1H, m); 7.05 (1H, m); 3.95 (2H, t); 3.75 (4H, m); 3.55 (4H, m); 3.0 (2H, br); 2.43 (1H, m); 1.65 (2H, m); 1.58 (2H, m); 1.15 (2H, m); 0.95 (3H, t). LCMS (M+1): 449.

Workup

  1. customthe solvent was removed by rotary evaporation
  2. customto give an oil
  3. waitAfter 1 hour
  4. customthe reaction was purified by prep-HPLC (pH10)
  5. customseparation gradient

Sources & evidence

ORD record
ord-186072d059454b839ff9b138f85f81b4
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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